Health Technology Assessment Research Articles

Artificial intelligence software for analysing chest X-ray images to identify suspected lung cancer: an evidence synthesis early value assessment.

Lung cancer is one of the most common types of cancer in the United Kingdom. It is often diagnosed late. The 5-year survival rate for lung cancer is below 10%. Early diagnosis may improve survival. Software that has an artificial intelligence-developed algorithm might be useful in assisting with the identification of suspected lung cancer. This review sought to identify evidence on adjunct artificial intelligence software for analysing chest X-rays for suspected lung cancer, and to develop a conceptual cost-effectiveness model to inform discussion of what would be required to develop a fully executable cost-effectiveness model for future economic evaluation. The data sources were MEDLINE All, EMBASE, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, Epistemonikos, ACM Digital Library, World Health Organization International Clinical Trials Registry Platform, clinical experts, Tufts Cost-Effectiveness Analysis Registry, company submissions and clinical experts. Searches were conducted from 25 November 2022 to 18 January 2023. Rapid evidence synthesis methods were employed. Data from companies were scrutinised. The eligibility criteria were (1) primary care populations referred for chest X-ray due to symptoms suggestive of lung cancer or reasons unrelated to lung cancer; (2) study designs that compared radiology specialist assessing chest X-ray with adjunct artificial intelligence software versus radiology specialists alone and (3) outcomes relating to test accuracy, practical implications of using artificial intelligence software and patient-related outcomes. A conceptual decision-analytic model was developed to inform a potential full cost-effectiveness evaluation of adjunct artificial intelligence software for analysing chest X-ray images to identify suspected lung cancer. None of the studies identified in the searches or submitted by the companies met the inclusion criteria of the review. Contextual information from six studies that did not meet the inclusion criteria provided some evidence that sensitivity for lung cancer detection (but not nodule detection) might be higher when chest X-rays are interpreted by radiology specialists in combination with artificial intelligence software than when they are interpreted by radiology specialists alone. No significant differences were observed for specificity, positive predictive value or number of cancers detected. None of the six studies provided evidence on the clinical effectiveness of adjunct artificial intelligence software. The conceptual model highlighted a paucity of input data along the course of the diagnostic pathway and identified key assumptions required for evidence linkage. This review employed rapid evidence synthesis methods. This included only one reviewer conducting all elements of the review, and targeted searches that were conducted in English only. No eligible studies were identified. There is currently no evidence applicable to this review on the use of adjunct artificial intelligence software for the detection of suspected lung cancer on chest X-ray in either people referred from primary care with symptoms of lung cancer or people referred from primary care for other reasons. Future research is required to understand the accuracy of adjunct artificial intelligence software to detect lung nodules and cancers, as well as its impact on clinical decision-making and patient outcomes. Research generating key input parameters for the conceptual model will enable refinement of the model structure, and conversion to a full working model, to analyse the cost-effectiveness of artificial intelligence software for this indication. This study is registered as PROSPERO CRD42023384164. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135755) and is published in full in Health Technology Assessment; Vol. 28, No. 50. See the NIHR Funding and Awards website for further award information.

RWE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 16.

In this update, we discuss recent US FDA guidance offering more specific guidelines on appropriate study design and analysis to support causal inference for non-interventional studies and the launch of the European Medicines Agency(EMA) and the Heads of Medicines Agencies (HMA) public electronic catalogues. We also highlight an article recommending assessing data quality and suitability prior to protocol finalization and a Journal of the American Medical Association-endorsed framework for using causal language when publishing real-world evidence studies. Finally, we explore the potential of large language models to automate the development of health economic models.

Organizational impact of systemic implementation of digital breast tomosynthesis as a primary test for breast cancer screening in Italy.

We present a comprehensive investigation into the organizational, social, and ethical impact of implementing digital breast tomosynthesis (DBT) as a primary test for breast cancer screening in Italy. The analyses aimed to assess the feasibility of DBT specifically for all women aged 45-74, women aged 45-49 only, or those with dense breasts only. Questions were framed according to the European Network of Health Technology Assessment (EuNetHTA) Screening Core Model to produce evidence for the resources, equity, acceptability, and feasibility domains of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) decision framework. The study integrated evidence from the literature, the MAITA DBT trials, and Italian pilot programs. Structured interviews, surveys, and systematic reviews were conducted to gather data on organizational impact, acceptability among women, reading and acquisition times, and the technical requirements of DBT in screening. Implementing DBT could significantly affect the screening program, primarily due to increased reading times and the need for additional human resources (radiologists and radiographers). Participation rates in DBT screening were similar, if not better, to those observed with standard digital mammography, indicating good acceptability among women. The study also highlighted the necessity for specific training for radiographers. The interviewed key persons unanimously considered feasible tailored screening strategies based on breast density or age, but they require effective communication with the target population. An increase in radiologists' and radiographers' workload limits the feasibility of DBT screening. Tailored screening strategies may maximize the benefits of DBT while mitigating potential challenges.

Health Technology Assessment for Fast-Track Elective Knee and Hip Arthroplasty in a High-Volume Orthopaedic Hospital in Italy.

The objective of the analysis presented is to assess the efficacy of a fast-track pathway for elective hip and knee arthroplasty, compared to the traditional approach, adopted within a research hospital located in Milan (Italy), in terms of length of stay reduction and related direct medical costs. A monocentric observational retrospective study was implemented considering adult subjects who underwent elective primary total hip or knee replacement, with a diagnosis of primary or secondary osteoarthritis. Exclusion criteria were subjects admitted via emergency department, subjects undergoing knee or hip replacement because of fractures or prosthesis revision. The analysis compared the length of stay and the direct medical costs, assuming the hospital perspective, of subjects admitted in the pre-fast-track period (years 2016/2017) and during the fast-track period (years 2018/2019). Knee replacement mean costs are 5,599 € (±1,158.3 €) in the pre-fast-track period and 4,487 € (±978.4 €) in the fast-track period (-1,112 €; -19.9%). Hip replacement mean costs in the pre-fast-track period are 5,364 € (±1,037.2 €) and 4,450 € (±843.7 €) in the fast-track period (-914 €; -17.0%). The adoption of fast-track pathway led to a statistically significant decrease of days of hospitalization of -2.8 (-37.6%) in knee replacement and of -2.9 (-39.2%) in hip replacement. The fast-track pathway adopted proved to be effective, reducing patients' length of stay, and sustainable and efficient, reducing direct medical costs, for both elective hip and knee replacement surgeries.

Early health technology assessment of gene silencing therapies for lowering lipoprotein(a) in the secondary prevention of coronary heart disease

Olpasiran and pelacarsen are gene-silencing therapies that lower lipoprotein(a). Cardiovascular outcome trials are ongoing. Mendelian randomisation studies estimated clinical benefits from lipoprotein(a) lowering. Our study estimated prices at which olpasiran and pelacarsen, in addition to standard-of-care, would be deemed cost-effective in reducing risk of recurrent coronary heart disease (CHD) events in the Australian healthcare system. We developed a decision tree and lifetime Markov model. For olpasiran, participants had CHD and lipoprotein(a) 260 nmol/L at baseline and three-monthly injections, profiled on OCEAN(a) Outcomes trial (NCT05581303). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a) from treatment. Mendelian randomisation study data were used to estimate downstream clinical benefits. Annual discounting was 5 %. For pelacarsen, participants had CHD and lipoprotein(a) 226 nmol/L at baseline and one- monthly injections, profiled on Lp(a) HORIZON (NCT04023552) trial. Olpasiran in addition to standard-of-care saved 0.87 discounted quality-adjusted life years (QALYs) per person. Olpasiran in addition to standard-of-care would be cost- effective at annual prices of AU$1867 (AU$467 per dose) at threshold AU$28,000 per QALY. Pelacarsen would be cost-effective at annual prices of AU$984 (AU$82 per dose). For ICER threshold AU$50,000 per QALY, olpasiran and pelacarsen would be cost-effective at annual prices AU$4207 and AU$2464 respectively. This early health technology assessment model used inclusion criteria from clinical trials. Olpasiran and pelacarsen would be cost-effective if annual treatment prices were AU$1867 and AU$984 respectively, from the Australian healthcare perspective.

Considerations for US coverage and reimbursement: Which digital health products to evaluate? Findings from a modified Delphi study.

The rapid growth of digital health tools, including digital applications, wearables, sensors, diagnostics, digital therapeutics (DTx), and prescription DTx, offers new ways to treat patients and close gaps in care. Payers need transparent, credible, and efficient processes to differentiate products for potential reimbursement from the larger universe of digital health products. To identify areas of agreement, disagreement, and rationale for payers to determine which digital health products should be evaluated for formulary consideration and to develop generalizable criteria for health care decision-makers developing policies and approaches for digital health products. Experts from the Academy of Managed Care Pharmacy DTx Advisory Group Payer Evaluation subcommittee rated whether a pharmacy and therapeutics committee, health technology assessment group, or an innovation center within a health plan or pharmacy benefit manager should consider 14 hypothetical products for potential formulary coverage. Using a 4-step modified Delphi approach, experts rated whether it was appropriate for a payer to evaluate each product on a scale of 1 (strongly disagree) to 9 (strongly agree). Quantitative agreement was assessed using terciles of responses, medians, and the distribution of appropriateness scores. The corresponding discussions are summarized to identify generalizable criteria for payers to consider as they develop approaches to determine which digital health products to evaluate. Among the 14 hypothetical products, 4 achieved quantitative agreement that payers should evaluate the product. 5 products had quantitative disagreement, and the remaining were indeterminant. Payers were most likely to review a product if it (1) was reviewed by the US Food and Drug Administration, (2) required a prescription, (3) was intended to be paid for using premium dollars, (4) treated rather than diagnosed or monitored a clinical condition, (5) had a low clinical opportunity cost, and (6) could address population health metrics. The rapid availability of digital health and DTx options can be daunting for health care decision-makers when determining which products to evaluate. These generalizable criteria can help payers develop a more efficient process.

The carbon footprint of external beam radiotherapy and its impact in health technology assessment

BackgroundThe major drivers of carbon dioxide (CO2eq) emissions of external beam radiation therapy (EBRT) are not well known and limit our ability to initiate mitigation strategies. Material and methodsWe describe the carbon footprint of four typical centers. We explore direct EBRT associated factors such as the impact of fractionation and use of MRI-LINAC, as well as indirect factors (e.g. patient rides). Treatment strategy related CO2eq emissions are included in a health technology assessment analysis that takes into account CO2eq emissions. ResultsA typical EBRT treatment emits from 185 kgCO2eq to 2066 kgCO2eq. CO2eq emissions are mostly driven by (i) accelerator acquisition and maintenance (37.8 %), (ii) patients and workers rides (32.7 %), (iii) drugs and medical devices (7.3 %), (iv) direct energy consumption (6.1 %), and (v) building and bunker construction (5.6 %) with a substantial heterogeneity among centers. Hypofractionation has a strong impact to mitigate emissions. MRI-LINAC is associated with a substantial increase in CO2eq emissions per fraction and requires ultra hypofractionation in 5 fractions to achieve a similar carbon footprint compared to 20 fractions treatment schemes. The expected limited small increase in toxicities due to hypofractionation (when existing) are in the same range as avoided detrimental effects to future people’s health thanks to CO2eq mitigation. ConclusionCarbon footprint of EBRT is not neglectable and could be mitigated. When safely feasible, hypofractionation is one of the main factors to decrease this impact. Taking into account CO2eq emissions has a substantial impact on the health technology assessment of EBRT, favoring hypofractionated regimens.

A Health Technology Assessment Perspective on Communicating Local Knowledge of Hippolite O. Amadi et al.'s Neonatal Interventions in Global Health Research

Background: This study employed a health technology assessment approach to explore the impact of Hippolite O. Amadiet al.’s neonatal care interventions. Methods: The research design was a qualitative desk research method. The purposive sampling procedure was adopted focusing on a subset of 10 out of a population of 45 journal articles authored by Amadi and others. Textual analysis was the method of data collection and interpretation analysis was used to analyze the data. Results: Locally tailored interventions such as the ‘handy approach’ temperature control, Neonatal Rescue Scheme, PoliteO2blend®, community-integrated neonatal care, Initial-Setpoint-Algorithm, weatherproof nursery designs, and the recycled incubator technique. These health technology interventions, designed to address challenges in low- and middle-income countries like Nigeria, underscored the significance of locally derived solutions in improving neonatal health outcomes. Conclusion: The study advocated for leveraging scientific journals as a pivotal medium for health technology assessment and science communication, facilitating the seamless exchange of local knowledge and innovations in neonatal care. By highlighting Hippolite Amadi’s research publications, the research emphasized the transformative role of journals in disseminating local innovations globally, promoting collaboration, and knowledge exchange beyond geographical boundaries. Recommendation: This study underscored the importance of active stakeholder involvement in optimizing neonatal outcomes through effective science communication, with a focus on prioritizing journals to facilitate the dissemination of local innovations on a global scale and foster collaboration among healthcare professionals, researchers, and local communities to address unique challenges faced by low- and middle-income countries in neonatal care practices.

'Twenty years of network meta-analysis: Continuing controversies and recent developments': A health technology assessment perspective.

We respond to some of the methodological issues raised in a recent review of network meta-analysis (NMA). We also provide a health technology developer's perspective and consider the future application of NMA to health technology assessment.

Adverse drug events in cost-effectiveness models of pharmacological interventions for diabetes, diabetic retinopathy, and diabetic macular edema: a scoping review.

The objective of this review was to examine the role of adverse drug events (ADEs) caused by pharmacological interventions in cost-effectiveness models for diabetes mellitus, diabetic retinopathy, and diabetic macular edema. Guidelines for economic evaluation recognize the importance of including ADEs in the analysis, but in practice, consideration of ADEs in cost-effectiveness models seem to be vague. Inadequate inclusion of these harmful outcomes affects the reliability of the results, and the information provided by economic evaluation could be misleading. Reviewing whether and how ADEs are incorporated in cost-effectiveness models is necessary to understand the current practices of economic evaluation. Studies included were published between 2011-2022 in English, representing cost-effectiveness analyses using modeling framework for pharmacological interventions in the treatment of diabetes mellitus, diabetic retinopathy, or diabetic macular edema. Other types of analyses and other types of conditions were excluded. The databases searched included MEDLINE (PubMed), CINAHL (EBSCOhost), Scopus, Web of Science Core Collection, and NHS Economic Evaluation Database. Gray literature was searched via the National Institute for Health and Care Excellence, European Network for Health Technology Assessment, the National Institute for Health and Care Research, and the International Network of Agencies for Health Technology Assessment. The search was conducted on January 1, 2023. Titles and abstracts were screened for inclusion by 2 independent reviewers. Full-text review was conducted by 3 independent reviewers. A data extraction form was used to extract and analyze the data. Results were presented in tabular format with a narrative summary, and discussed in the context of existing literature and guidelines. A total of 242 reports were extracted and analyzed in this scoping review. For the included analyses, type 2 diabetes was the most common disease (86%) followed by type 1 diabetes (10%), diabetic macular edema (9%), and diabetic retinopathy (0.4%). The majority of the included analyses used a health care payer perspective (88%) and had a time horizon of 30 years or more (75%). The most common model type was a simulation model (57%), followed by a Markov simulation model (18%). Of the included cost-effectiveness analyses, 26% included ADEs in the modeling, and 13% of the analyses excluded them. Most of the analyses (61%) partly considered ADEs; that is, only 1 or 2 ADEs were included. No difference in overall inclusion of ADEs between the different conditions existed, but the models for diabetic retinopathy and diabetic macular edema more often omitted the ADE-related impact on quality of life compared with the models for diabetes mellitus. Most analyses included ADEs in the models as probabilities (55%) or as a submodel (40%), and the most common source for ADE incidences were clinical trials (65%). The inclusion of ADEs in cost-effectiveness models is suboptimal. The ADE-related costs were better captured than the ADE-related impact on quality of life, which was most pronounced in the models for diabetic retinopathy and diabetic macular edema. Future research should investigate the potential impact of ADEs on the results, and identify the criteria and policies for practical inclusion of ADEs in economic evaluation.

Designing a Roadmap for Health Technology Assessment Implementation in Algeria.

Background The scarcity of resources restricts healthcare financing decisions, affecting the population's health. Health technology assessment (HTA) balances restricted budgets with the best possible health outcomes. We aim to characterize the current status of HTA in Algeria and describe the future directions for HTA implementation according to the priorities set by local stakeholders. Methods Stakeholders from the public and private sectors responded to a policy survey about the current and preferred future status of HTA implementation in Algeria. The survey was administered during an online workshop and used a widely accepted international scorecard covering eight domains: capacity building, HTA financing, process and organizational structure, scope of HTA implementation, decision criteria, standardization of methodology, use of local data, and international collaboration. After that, one-on-one interviews with another local expert were conducted to validate and modify the draft recommendations. The interviewees were representatives from government agencies, hospitals, and pharmaceutical companies. Results Thirty-one experts filled out the HTA scorecard survey; most of them were from the public sector (74%). They highlighted that project-based HTA workshops or short courses were the most common form of HTA education in Algeria and recommended the establishment of postgraduate HTA training programs in the future to build sustainable capacities. They reported a lack of funding for HTA research and critical appraisal and recommended an increased public budget for HTA and the introduction of submission fees by manufacturers. There was consensus about the need for local HTA evidence generation in the future. Most of the experts advocated an explicit soft decision threshold. The interviewees further recommended using multi-criteria decision analysis in the short term. The application of quality indicators was believed to improve the reliability of the HTA process. Conclusion The results of our policy research delineate the gap between the current and preferred future status of HTA in Algeria based on insights from multiple stakeholders. The need to improve the educational HTA programs in Algeria, use local data in policy decisions, and increase funding for HTA were the most advocated recommendations.

Machine Learning Methods to Estimate Individualized Treatment Effects for Use in Health Technology Assessment.

Recent developments in causal inference and machine learning (ML) allow for the estimation of individualized treatment effects (ITEs), which reveal whether treatment effectiveness varies according to patients' observed covariates. ITEs can be used to stratify health policy decisions according to individual characteristics and potentially achieve greater population health. Little is known about the appropriateness of available ML methods for use in health technology assessment. In this scoping review, we evaluate ML methods available for estimating ITEs, aiming to help practitioners assess their suitability in health technology assessment. We present a taxonomy of ML approaches, categorized by key challenges in health technology assessment using observational data, including handling time-varying confounding and time-to event data and quantifying uncertainty. We found a wide range of algorithms for simpler settings with baseline confounding and continuous or binary outcomes. Not many ML algorithms can handle time-varying or unobserved confounding, and at the time of writing, no ML algorithm was capable of estimating ITEs for time-to-event outcomes while accounting for time-varying confounding. Many of the ML algorithms that estimate ITEs in longitudinal settings do not formally quantify uncertainty around the point estimates. This scoping review may not cover all relevant ML methods and algorithms as they are continuously evolving. Existing ML methods available for ITE estimation are limited in handling important challenges posed by observational data when used for cost-effectiveness analysis, such as time-to-event outcomes, time-varying and hidden confounding, or the need to estimate sampling uncertainty around the estimates. ML methods are promising but need further development before they can be used to estimate ITEs for health technology assessments. Estimating individualized treatment effects (ITEs) using observational data and machine learning (ML) can support personalized treatment advice and help deliver more customized information on the effectiveness and cost-effectiveness of health technologies.ML methods for ITE estimation are mostly designed for handling confounding at baseline but not time-varying or unobserved confounding. The few models that account for time-varying confounding are designed for continuous or binary outcomes, not time-to-event outcomes.Not all ML methods for estimating ITEs can quantify the uncertainty of their predictions.Future work on developing ML that addresses the concerns summarized in this review is needed before these methods can be widely used in clinical and health technology assessment-like decision making.

Future support on evidence-informed priority setting and situational analysis of the potential role of Health Technology Assessment in Africa to support future pandemic preparedness and response: protocol for a scoping review

BackgroundThe COVID-19 pandemic has highlighted the importance of evidence-informed priority setting and situational analysis in pandemic preparedness and response. Health Technology Assessment (HTA) has been identified as an essential tool for evidence-informed decision-making in healthcare. However, the potential role of HTA in pandemic preparedness and response in Africa has yet to be explored. The objective of this scoping review is to ascertain the current understanding of the possible role of HTA in Africa to support future pandemic preparedness and response.MethodsWe will conduct a scoping review of literature published between 2010 and 2024. Electronic databases like Embase, PubMed, Scopus, Web of Science, and Google Scholar will be utilized to perform the search. We will also search grey literature sources such as websites of relevant organizations and government agencies. The search will only include studies that were conducted in the English language. Two reviewers will evaluate the titles and abstracts of the publications independently to determine their eligibility using Covidence. Full-text articles will be reviewed for eligibility and data extraction. The data will be extracted using a standardized form. The extracted data will include information on the study design, objectives, methods, findings, and conclusions. The thematic analysis approach will guide the data analysis. Themes and sub-themes will be identified and reported. The review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines.DiscussionThis scoping review will identify the existing knowledge on the potential role of HTA in Africa to support future pandemic preparedness and response. The findings will aid in identifying deficiencies in knowledge and provide valuable insights for future study. Additionally, they will inform policy-makers and other stakeholders about the potential contribution of the Health Technology Assessment (HTA) in enhancing Africa’s readiness and response to pandemics.

Systematic Review of Economic Evaluations of Systemic Treatments for Advanced and Metastatic Gastric Cancer.

Recent advances in the development of biomarker-directed therapy and immunotherapy, for advanced and metastatic gastric cancers, have the potential to improve survival and quality of life.Much attention has been directed towards second- and later-line treatments, and the landscape here is evolving rapidly. However, uncertainty in relative effectiveness, high costs and uncertainty in cost effectiveness represent challenges for decision makers. To identify economic evaluations for the second-line or later-line treatment of advanced and metastatic gastric cancer. Also, to assess key criteria (including model assumptions, inputs and outcomes), reporting completeness andmethodological quality to inform future cost-effectiveness evaluations. A systematic literature search (from database inception to 5 March 2023) of EconLit via EBSCOhost, Cochrane Library (restricted to National Health Service [NHS] Economic Evaluation Database and Health Technology Assessment [HTA] Database), Embase, MEDLINE and of grey literature was conducted. This aimed to identify systemic treatments that align with National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) Clinical Practice Guidelines. Data were collected on key criteria and on reporting completeness and methodological quality. A narrative synthesis focussed on cost-effectiveness and cost-of-illness studies. Outcomes of interest included total and incremental costs and outcomes (life-years and quality-adjusted life-years), ratios of incremental costs per unit outcome and other summary cost and outcome measures. Also, for cost-effectiveness studies, reporting completeness and the methodological quality were assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and the Philips Checklist, respectively. A total of 19 eligible economic evaluations were identified (cost-effectiveness studies [n = 15] and cost-of-illness studies [n = 4]). There was a general lack of consistency in the methodological approaches taken across studies. In the main, the cost-effectiveness studies indicated that the intervention under consideration was more effective and more costly than the comparator(s). However, most interventions were not cost effective. No studies were fully compliant with reporting-completeness and methodological-quality requirements. Given the lack of consistency in the approaches taken across cost-of-illness studies, outcomes could not be directly compared. To our knowledge, this is the first published systematic literature review that has qualitatively synthesised economic evaluations for advanced and metastatic gastric cancer. There were differences in the approaches taken across the cost-effectiveness studies and the cost-of-illness studies. The conclusions of most of the cost-effectiveness studies were consistent despite identified differences in approaches. In the main, the interventions under consideration were not cost effective, presenting challenges to sustainability and affordability. We highlight a requirement for cost-effectiveness evaluations and for second-line or later-line treatments of advanced and metastatic gastric cancer that consider all relevant comparators and that are compliant with reporting-completeness and methodological-quality requirements. By addressing the methodological gaps identified here, future healthcare decision-making, within the context of this rapidly changing treatment landscape, would be better informed. CRD42023405951.

The Polish Society of Gynecological Oncology Guidelines for the Diagnosis and Treatment of Cervical Cancer (v2024.0).

Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages.

HTA model for laboratory medicine technologies: overview of approaches adopted in some international agencies.

The Health Technology Assessment (HTA) Working Group of the Emerging Technology Division of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) aims to develop a methodological approach for producing structured HTA information for laboratory medicine technologies. This approach seeks to support decision-making processes at the country, regional, and/or hospital levels regarding the introduction of specific technologies. The focus of this model will primarily be ondefining assessment elements within the domains of 'organizational aspects' and 'costs and economic evaluations', potentially differentiated by the type of diagnostic technology (e.g., genetic tests, molecular tests). To achieve this project's goal, a literature review and examination ofwebsites of international HTA agencies have been conducted. The research aims to identify multidisciplinary methodological approaches used to assess laboratory diagnostic technologies and to pinpoint the domains and assessment elements utilized. Wefound 7 methodological articles describing methodological approaches adopted toassess laboratory diagnostic technologies. Among the HTA organizations considered, 23 reports were found, of which 7 were produced by the European Network of HTA (EUnetHTA), 4 by the National Institute for Health and Care Excellence Diagnostic Assessment Program (NICE DAP), and 12 by other HTA agencies. The EUnetHTA reports wererapid collaborative assessments covering various domains, while the NICE DAP reports focused on diagnostic guidances, including descriptions of technologies, clinical need and practice, diagnostic tests, accuracy, effectiveness, and cost-effectiveness. Finally, a survey targeting laboratory professionals will be conducted to introduce assessment elements, differentiated by the type of diagnostic technology, primarily for organizational and economic domains.

Can SMA Innovative Treatments Be Reimbursed? A Rapid Review

Context: Spinal muscular atrophy (SMA) is a rare genetic disorder that significantly impacts the quality of life. This paper aims to gather current understanding of the safety, efficacy, and economic aspects of common SMA treatments to assist Iranian policymakers in adopting these novel treatments for this vulnerable population. Methods: This rapid health technology assessment (HTA) research was conducted in four steps: Database review, screening, data extraction, and thematic analysis. Inclusion criteria consisted of studies focused on assessing the safety, efficacy, and economic aspects of medical interventions in SMA patients compared to those who did not receive such interventions. Results: Based on current data, nusinersen was found to be the most effective treatment (increasing mobility achievements in SMA types 1 and 2) with the least side effects for SMA types 1 and 2. In terms of economic evaluations, none of the treatments were found to be cost-effective. Conclusions: The decision regarding reimbursement for such medical drugs should not focus solely on their cost-effectiveness but rather on creating access to essential care, meeting patient needs, and considering national budget limitations. Managed entry agreements (MEAs) are flexible tools that service providers or payers can use to negotiate and reduce the financial burden for both patients and payers.

Domains and Methods of Medical Device Technology Evaluation: A Systematic Review.

Identify, through a systematic review, the main domains and methods to support health technology assessment of Medical Devices (MD) from the perspective of technological incorporation into healthcare systems. Performed structured searches in MEDLINE, Embase, BVS, Cochrane Library, and Web of Science for full studies published between 2017 and May 2023. Selection, extraction, and quality assessment were performed by two blinded reviewers, and discrepancies were resolved by a third reviewer. A total of 5,790 studies were retrieved, of which 41 were included. We grouped the identified criteria into eight domains for the evaluations. Overall, studies discuss the need to establish specific methods for conducting HTA in MD. Due to the wide diversity of MD types, a single methodological guideline may not encompass all the specificities and intrinsic characteristics of the plurality of MD. Studies suggest using clustering criteria through technological characterization as a strategy to make the process as standardized as possible.

Long-term effects of once-only flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: 21-year follow-up of the UK Flexible Sigmoidoscopy Screening randomised controlled trial

Flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality; however, uncertainty exists about the duration of protection and differences by sex and age. We assessed effects of once-only flexible sigmoidoscopy screening after 21 years' follow-up. The UK Flexible Sigmoidoscopy Screening Trial is a multicentre randomised controlled trial that recruited men and women aged 55-64 years from general practices serving 14 hospitals. Among participants indicating that they would attend flexible sigmoidoscopy screening if invited, randomisation (2:1) to the control (no further contact) or intervention (invited to once-only flexible sigmoidoscopy screening) group was performed centrally in blocks of 12, stratified by centre, general practice, and household type. Masking of intervention was infeasible. Primary outcomes were colorectal cancer incidence and mortality. The Kaplan-Meier method estimated cumulative incidence. Primary analyses estimated intention-to-treat hazard ratios (HRs) and risk differences, overall and stratified by subsite, sex, and age. The trial is registered with ISRCTN, number 28352761. Among participants recruited between Nov 14, 1994, and March 30, 1999, 170 432 were eligible and 113 195 were randomly assigned to the control group and 57 237 were randomly assigned to the intervention group. 406 participants were excluded from analyses (268 in the control group and 138 in the intervention group), leaving 112 927 participants in the control group (55 336 [49%] men and 57 591 [51%] women) and 57 099 in the intervention group (27 966 [49%] men and 29 103 [51%] women). Of participants who were invited to be screened, 40 624 (71%) attended screening. Median follow-up was 21·3 years (IQR 18·0-22·2). In the invited-to-screening group, colorectal cancer incidence was reduced compared with the control group (1631 vs 4201 cases; cumulative incidence at 21 years was 3·18% [95% CI 3·03 to 3·34] vs 4·16% [4·04 to 4·29]; HR 0·76 [95% CI 0·72 to 0·81]) with 47 fewer cases per 100 000 person-years (95% CI -56 to -37). Colorectal cancer mortality was also reduced in the invited-to-screening group compared with the control group (502 vs 1329 deaths; cumulative incidence at 21 years was 0·97% [0·88 to 1·06] vs 1·33% [1·26 to 1·40]; HR 0·75 [0·67 to 0·83]) with 16 fewer deaths per 100 000 person-years (-21 to -11). Effects were particularly evident in the distal colorectum (726 incident cancer cases in the invited-to-screening group vs 2434 cases in the control group; HR 0·59 [0·54 to 0·64]; 47 fewer cases per 100 000 person-years [-54 to -41]; 196 cancer deaths in the invited-to-screening group vs 708 deaths in the control group; HR 0·55 [0·47 to 0·64]; 15 fewer deaths per 100 000 person-years [-19 to -12]) and not the proximal colon (871 incident cancer cases in the invited-to-screening group vs 1749 cases in the control group; HR 0·98 [0·91 to 1·07]; one fewer case per 100 000 person-years [-8 to 5]; 277 cancer deaths in the invited-to-screening group vs 547 deaths in the control group; HR 1·00 [0·86 to 1·15]; zero fewer deaths per 100 000 person-years [-4 to 4]). The HR for colorectal cancer incidence was lower in men (0·70 [0·65-0·76]) than women (0·86 [0·79 to 0·93]; pinteraction=0·0007) but there was no difference by age. We show that once-only flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality for two decades and provide important data to inform colorectal cancer screening guidelines. National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.

Priority areas for the development of the health technology assessment system in Ukraine: survey results

The purpose of the study is to analyze the expert opinion on the priority areas of development of the HTA in Ukraine, taking into account the existing condition, problems and possible prospects for effective development. Materials and methods. The expert survey (online questionnaire) included the preparation of a special questionnaire, targeted selection of experts based on their competence in the field of HTA. Three groups of respondents took part in the survey, including 13 HTA developers, 32 users, and 31 informed persons to ensure the representativeness of the survey results. The following methods were used to process and interpret the results: scientific generalization, mathematical and statistical, analytical, and graphical. Results of the study. Based on the results of the expert survey, the role and place of the HTA in the health care system was determined. Experts see the main purpose of the HTA as preparing the necessary information of the relevant level of evidence for decision-making on the selection of optimal MTs (in particular, for budget procurement, inclusion in regulatory lists for price regulation and reimbursement). The respondents' opinions on the participation of different socio-professional groups in the implementation of the HTA and the use of its results were studied. Thus, according to the results of the survey, HTA experts and scientists can carry out the assessment, and in some cases (mini-HTA, hospital HTA for the formation of local formularies and protocols) – specialists of medical institutions. According to the respondents, it is advisable to expand the use of HTA results for decision-making at the national, regional and local levels. According to the survey, the priority areas for the development of HTA are the creation of a professional environment, adequate logistical and informational support, improvement of legislation, creation of an optimal institutional structure, harmonization of HTA methodology and development of international cooperation. Conclusions. The expert survey allowed us to determine the most likely scenario for the further development of HTA in Ukraine. According to the majority of respondents, the main efforts are currently focused on capacity building, formation of a professional environment, active use of evidence, and infrastructure development.